Steroid Hormone Receptors

Question 1

What does “not all ligands are steroids” mean?

Answer 1

Not all ligands are cholesterol derivatives

Question 2

What ligands are cholesterol derivatives?

Answer 2

• cortisol
• estradiol
• testosterone
• aldosterone

Question 3

What is the function of carrier proteins?

Answer 3

helps get signal molecule widespread throughout body

Question 4

Most important carrier protein for cortisol?

Answer 4

transcortin

Question 5

Most important carrier for thyroid hormone?

Answer 5

thyroxine-binding-globulin

Question 6

Members of the steroid hormone receptor superfamily all contain what structures?

Answer 6

• transcription-activating domain
• DNA binding domain
• hormone-binding domain

Question 7

Common signaling mechanism for steroid hormone receptors

Answer 7

• DNA-binding site is hidden by an inhibitory protein complex.
• The steroid hormone enters and binds to its receptor
• The inhibitory protein releases and the DNA-binding site is now exposed

Question 8

Examples of steroid hormone receptors in the cytosol

Answer 8

• glucocorticoid receptors

- aldosterone receptors

Question 9

Examples of receptors in the nucleus

Answer 9

• thyroid hormone receptor

- vit. D3 receptor

Question 10

Specificity of Signaling

Answer 10

• cell must contain receptor
• specific set of gene regulatory proteins must be present in order to activate transciprtion
• some gene regulatory proteins are cell specific

Question 11

Is signaling via intracellular receptors fast or slow? Why?

Answer 11

Slow = approx. 10 minutes at the fastest

Why?

• Long diffusion paths for ligand. Carrier proteins present a reservoir for ligands (=signal molecules)
• Effect requires transcription and translation
• Termination requires excretion of hormone (often as bile after conjugation in the liver)

Question 12

Mineralocorticoid Receptor

Answer 12

Hormone: Aldosterone

Produced in response to decrease in blood pressure

Origin: Adrenal Cortex
-produced on demand - no storage!

Carrier protein: transcortin; albumin

ReceptorL Mineralocorticoid receptor

Effect:
-In Kidney: Na+ and H2O retention (and K+ excretion) leading to increase in blood pressure

Question 13

What is renin?

Answer 13

An enzyme released by the kidney that helps lead to increase in blood pressure as a response to a drop in blood pressure

Question 14

Why are ligands bound to carrier proteins in the blood stream?

Answer 14

Prevents excretion in the kidney

Question 15

How long can ligands remain in the blood stream until they are excreted?

Answer 15

Hours (a relatively long time)

Question 16

Thyroid Hormone Receptor

Answer 16

Hormone: Tri-iodo-thyronie (T3)

Released in response to cold and stress

Origin: Thyroid gland synthesizes and stores prohormone thyroxine (T4) from which one iodine is removed to generate T3

Carrier protein: Thyroxine-binding prealbumin, thyroxine-binding globulin

Receptor: thyroid hormone receptor

Effect:

• general increase in metabolism
• increased O2 consumption and ventilation
• thermogenesis
• mobilization of fat and protein

Question 17

How does prohormone thyroxine, T4, play into the production of T3?

Answer 17

T4 is produced and stored in the thyroid gland. One iodine is removed from T4 iin the kidney/liver to make T3

Question 18

TRH

Answer 18

thyrotropin releasing hormone

released by hypothalamus

Question 19

TSH

Answer 19

thyroid stimulating hormone = thyrotropin

released by pituitary

Question 20

Feline Hyperthyroidism

Answer 20

Presentation:

• weight loss, despite a good appetite
• rapid heat rate
• hyperexcitability
• vomiting/diarrhea
• poor hair coat

Diagnosis;

• rule out other diseases
• determination of plasma levels of T4

Prevalence:
-most common endocrine disorder in older cats

Suspected causes:

• cats living longer
• exposure to chemicels -> polybrominated diphenyl ethers (PBDEs- flame retardants)

Question 21

Etiology of Feline Hyperthyroidism

Answer 21

• most often caused by a thyroid adenoma
• only 2% of affected cats are diagnosed with thyroid adenocarcinoma
• one or both lobes of thyroid gland may be involved

Question 22

Treatment of Feline Hyperthyroidism

Answer 22

1. Methimazole (Tapazol) - inhibits T3/T4 production
2. Surgical removal of thyroid gland
3. Radio-iodine treatment with Iodine 131 (iodine 127 is the stable, non-radioactive isotope)

Question 23

Cats treated for feline hyperthyroidism with radio-iodine treatment need to remain in the hospital for 10-14 days post-treatment. Why?

Answer 23

• Iodine 131 has a half-life of 8 days

- Litter boxes are radioactive

Question 24

Phosphorylation

Answer 24

conformation change of proteins

Question 25

Which three amino acids contain -OH groups that are suitable for adding a phosphate group?

Answer 25

• Serine
• Threonine
• Tyrosine

Question 26

kinase

Answer 26

adds a phosphate group

“phosphorylation”

Question 27

phosphatase

Answer 27

takes a phosphate group off

“dephosphorylation”

Question 28

Serine/Threonine kinases

Answer 28

• Protein Kinase A = A-kinase
• Protein Kinase C = C-kinase
• Protein Kinase G = G-kinase
• Calmodulin-Activated Kinase = CaM Kinase
• Mitogen-Activated Protein Kinase = MAP-kinase

Question 29

Phosphatases involved in Phosphorylation

Answer 29

• Serine/Threonine Phopsphatases

- Tyrosine Phosphatase

Question 30

Tysosine kinases

Answer 30

ex - insulin receptor

• many growth factors
• SRC
• JAK